HTRA1 was considered as one of important age-related macular degeneration (AMD) candidate genes. However, due to population heterogeneity and bias from case-control study, the association between HTRA1 and AMD needs further confirmation across different studies in different population. In this study, a meta-analysis was performed in 14 case-control studies which were published before August 31, 2008. Effect of HTRA1 polymorphism with AMD was synthetically evaluated. The pooled odds ratio (OR) for heterozygous genotype GA versus wild homozygous genotype GG is 2.13 (95% CI: 1.90, 2.39), the OR of homozygous genotype AA versus GG is 6.92 (95% CI: 5.74, 8.34) and the OR of allele A carrier (GA+AA) versus GG is 3.02 (95% CI: 2.57, 3.53). Sub-analysis indicated that the risk of HTRA1 rs11200638 on wet AMD was stronger than dry AMD, and it seems that HTRA1 rs11200638 could increase the risk of AMD in all races. This study strengthens the hypothesis of association between rs11200638 in the promoter of HTRA1 polymorphism and AMD. The variant of HTRA1/625G-->A could be a potentially promising genetic biomarker of AMD.